title: Recurrence-free survival in prostate cancer is related to increased stromal TRAIL expression.
abstract: BACKGROUND
  TRAIL (tumor necrosis factor related apoptosis-inducing ligand) is involved in tumor immune surveillance and, thus, may be a potential cancer therapy. TRAIL expression in the tumor microenvironment has been shown to impact cancer survival in multiple tumor types, including ovarian cancer. We studied TRAIL expression and outcomes in patients with prostate cancer.
  
  
  METHODS
  A tissue microarray (TMA) of 200 prostate cancer patients and benign prostate tissue controls was used to assess the epithelial and stromal protein expression of TRAIL, death receptors (DR4 and DR5), decoy receptors (DcR1 and DcR2), and the FLICE inhibitory protein (FLIP(L) ). We correlated these expression patterns with clinicopathological parameters and determined its impact on recurrence-free survival.
  
  
  RESULTS
  Nearly all (99.5%) prostate cancer tissues examined displayed either decreased expression of pro-apoptotic TRAIL receptors, increased FLIP(L) expression, or both. We observed elevated death receptor, decoy receptor, FLIP(L) , and epithelial TRAIL expression in prostate cancer epithelium. TRAIL expression in the stromal tumor microenvironment surrounding the prostate cancer was markedly lower. Elevated TRAIL expression in the tumor microenvironment was also significantly associated with increased recurrence-free survival (P = .014), after controlling for other prognostic markers. In contrast, epithelial expression of TRAIL did not have an effect on overall survival.
  
  
  CONCLUSIONS
  Expression of the components of the pro-apoptotic TRAIL pathway is altered in prostate cancer. Moreover, TRAIL expression in the tumor microenvironment may affect recurrence-free survival rate of prostate cancer patients. Consequently, these results may be useful in devising future therapeutic strategies targeting the TRAIL pathway in prostate cancer.
authors.affiliation: Division of Oncology, Department of Medicine I, Medical University of Vienna, Vienna, Austria.
authors.forename: Mariam
authors.initials: M
authors.lastname: Anees
authors.forename: Peter
authors.initials: P
authors.lastname: Horak
authors.forename: Ahmed
authors.initials: A
authors.lastname: El-Gazzar
authors.forename: Martin
authors.initials: M
authors.lastname: Susani
authors.forename: Georg
authors.initials: G
authors.lastname: Heinze
authors.forename: Paul
authors.initials: P
authors.lastname: Perco
authors.forename: Massimo
authors.initials: M
authors.lastname: Loda
authors.forename: Rosina
authors.initials: R
authors.lastname: Lis
authors.forename: Michael
authors.initials: M
authors.lastname: Krainer
authors.forename: William K
authors.initials: WK
authors.lastname: Oh
mesh_terms: D053446:CASP8 and FADD-Like Apoptosis Regulating Protein / Q000378:metabolism; D002277:Carcinoma / Q000175:diagnosis / Q000378:metabolism* / Q000401:mortality* / Q000628:therapy*; D018572:Disease-Free Survival; D006801:Humans; D008297:Male; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000401:mortality* / Q000628:therapy*; D053218:Receptors, Death Domain / Q000378:metabolism; D012008:Recurrence; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology; D015996:Survival Rate; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism* / Q000502:physiology; D046888:Tissue Array Analysis; D059016:Tumor Microenvironment / Q000502:physiology; D015854:Up-Regulation / Q000502:physiology
chemical_list: D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D053218:Receptors, Death Domain; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human